TOM22_HUMAN
ID TOM22_HUMAN Reviewed; 142 AA.
AC Q9NS69;
DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Mitochondrial import receptor subunit TOM22 homolog;
DE Short=hTom22;
DE AltName: Full=1C9-2;
DE AltName: Full=Translocase of outer membrane 22 kDa subunit homolog;
GN Name=TOMM22; Synonyms=TOM22;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Liver;
RX PubMed=10982837; DOI=10.1128/mcb.20.19.7205-7213.2000;
RA Yano M., Hoogenraad N., Terada K., Mori M.;
RT "Identification and functional analysis of human Tom22 for protein import
RT into mitochondria.";
RL Mol. Cell. Biol. 20:7205-7213(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 24-31; 48-58; 61-76 AND
RP 107-135.
RC TISSUE=Myeloid leukemia cell;
RX PubMed=10900208; DOI=10.1074/jbc.m004794200;
RA Saeki K., Suzuki H., Tsuneoka M., Maeda M., Iwamoto R., Hasuwa H.,
RA Shida S., Takahashi T., Sakaguchi M., Endo T., Miura Y., Mekada E.,
RA Mihara K.;
RT "Identification of mammalian Tom22 as a subunit of the preprotein
RT translocase of the mitochondrial outer membrane.";
RL J. Biol. Chem. 275:31996-32002(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 2-22; 48-58 AND 61-76, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (JUN-2005) to UniProtKB.
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [8]
RP IDENTIFICATION IN THE TOM COMPLEX.
RX PubMed=18331822; DOI=10.1016/j.bbrc.2008.02.150;
RA Kato H., Mihara K.;
RT "Identification of Tom5 and Tom6 in the preprotein translocase complex of
RT human mitochondrial outer membrane.";
RL Biochem. Biophys. Res. Commun. 369:958-963(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-43, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-15, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE
RP ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-15, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE
RP ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: Central receptor component of the translocase of the outer
CC membrane of mitochondria (TOM complex) responsible for the recognition
CC and translocation of cytosolically synthesized mitochondrial
CC preproteins. Together with the peripheral receptor TOM20 functions as
CC the transit peptide receptor and facilitates the movement of
CC preproteins into the translocation pore (PubMed:10982837). Required for
CC the translocation across the mitochondrial outer membrane of cytochrome
CC P450 monooxygenases (By similarity). {ECO:0000250|UniProtKB:Q75Q41,
CC ECO:0000269|PubMed:10982837}.
CC -!- SUBUNIT: Forms part of the preprotein translocase complex of the outer
CC mitochondrial membrane (TOM complex) which consists of at least 7
CC different proteins (TOMM5, TOMM6, TOMM7, TOMM20, TOMM22, TOMM40 and
CC TOMM70) (PubMed:18331822). Interacts with TOMM40. Interacts with
CC PPP2R2B (By similarity). {ECO:0000250|UniProtKB:Q75Q41,
CC ECO:0000269|PubMed:18331822}.
CC -!- INTERACTION:
CC Q9NS69; Q13520: AQP6; NbExp=3; IntAct=EBI-1047508, EBI-13059134;
CC Q9NS69; P42858: HTT; NbExp=6; IntAct=EBI-1047508, EBI-466029;
CC Q9NS69; P13473-2: LAMP2; NbExp=3; IntAct=EBI-1047508, EBI-21591415;
CC Q9NS69; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-1047508, EBI-2623095;
CC Q9NS69; Q9P0U1: TOMM7; NbExp=2; IntAct=EBI-1047508, EBI-1180558;
CC Q9NS69; P0DOE7: M; Xeno; NbExp=2; IntAct=EBI-1047508, EBI-10042882;
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000269|PubMed:10982837}; Single-pass membrane protein
CC {ECO:0000269|PubMed:10982837}.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DOMAIN: Requires the transmembrane domain (TMD), a short segment (the
CC import sequence) in the cytoplasmic domain localizing separately from
CC the TMD and the C-tail signal in the C-terminal domain for efficient
CC targeting and integration into the TOM complex (By similarity). The N-
CC terminal domain (residues 1-62) is important for binding to the
CC unfolded mature imported proteins. Residues (49-71) of the cytoplasmic
CC domain interacts with TOMM20 while the C-terminal segment (residues 63-
CC 82) binds presequence of preproteins. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the Tom22 family. {ECO:0000305}.
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DR EMBL; AB040119; BAB03306.1; -; mRNA.
DR EMBL; AB041906; BAB16408.1; -; mRNA.
DR EMBL; AK024731; BAB14979.1; -; mRNA.
DR EMBL; CR456475; CAG30361.1; -; mRNA.
DR EMBL; BC009363; AAH09363.1; -; mRNA.
DR CCDS; CCDS13975.1; -.
DR RefSeq; NP_064628.1; NM_020243.4.
DR PDB; 7CK6; EM; 3.40 A; C/D=1-142.
DR PDB; 7CP9; EM; 3.00 A; G/H=1-142.
DR PDBsum; 7CK6; -.
DR PDBsum; 7CP9; -.
DR AlphaFoldDB; Q9NS69; -.
DR SMR; Q9NS69; -.
DR BioGRID; 121308; 396.
DR ComplexPortal; CPX-6121; TOM40 mitochondrial outer membrane translocase complex.
DR CORUM; Q9NS69; -.
DR IntAct; Q9NS69; 163.
DR MINT; Q9NS69; -.
DR STRING; 9606.ENSP00000216034; -.
DR iPTMnet; Q9NS69; -.
DR MetOSite; Q9NS69; -.
DR PhosphoSitePlus; Q9NS69; -.
DR BioMuta; TOMM22; -.
DR EPD; Q9NS69; -.
DR jPOST; Q9NS69; -.
DR MassIVE; Q9NS69; -.
DR MaxQB; Q9NS69; -.
DR PaxDb; Q9NS69; -.
DR PeptideAtlas; Q9NS69; -.
DR PRIDE; Q9NS69; -.
DR ProteomicsDB; 82500; -.
DR TopDownProteomics; Q9NS69; -.
DR Antibodypedia; 291; 123 antibodies from 28 providers.
DR DNASU; 56993; -.
DR Ensembl; ENST00000216034.6; ENSP00000216034.4; ENSG00000100216.6.
DR GeneID; 56993; -.
DR KEGG; hsa:56993; -.
DR MANE-Select; ENST00000216034.6; ENSP00000216034.4; NM_020243.5; NP_064628.1.
DR UCSC; uc003awe.4; human.
DR CTD; 56993; -.
DR GeneCards; TOMM22; -.
DR HGNC; HGNC:18002; TOMM22.
DR HPA; ENSG00000100216; Low tissue specificity.
DR MIM; 607046; gene.
DR neXtProt; NX_Q9NS69; -.
DR OpenTargets; ENSG00000100216; -.
DR PharmGKB; PA38275; -.
DR VEuPathDB; HostDB:ENSG00000100216; -.
DR eggNOG; KOG4111; Eukaryota.
DR GeneTree; ENSGT00390000016475; -.
DR HOGENOM; CLU_108175_1_0_1; -.
DR InParanoid; Q9NS69; -.
DR OMA; IKGLYAY; -.
DR OrthoDB; 1625053at2759; -.
DR PhylomeDB; Q9NS69; -.
DR TreeFam; TF106201; -.
DR PathwayCommons; Q9NS69; -.
DR Reactome; R-HSA-1268020; Mitochondrial protein import.
DR Reactome; R-HSA-5205685; PINK1-PRKN Mediated Mitophagy.
DR SignaLink; Q9NS69; -.
DR SIGNOR; Q9NS69; -.
DR BioGRID-ORCS; 56993; 742 hits in 1084 CRISPR screens.
DR ChiTaRS; TOMM22; human.
DR GeneWiki; TOMM22; -.
DR GenomeRNAi; 56993; -.
DR Pharos; Q9NS69; Tbio.
DR PRO; PR:Q9NS69; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q9NS69; protein.
DR Bgee; ENSG00000100216; Expressed in tendon of biceps brachii and 193 other tissues.
DR ExpressionAtlas; Q9NS69; baseline and differential.
DR Genevisible; Q9NS69; HS.
DR GO; GO:0016021; C:integral component of membrane; IDA:BHF-UCL.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; TAS:Reactome.
DR GO; GO:0005742; C:mitochondrial outer membrane translocase complex; IDA:BHF-UCL.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0008320; F:protein transmembrane transporter activity; ISS:BHF-UCL.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0045040; P:protein insertion into mitochondrial outer membrane; IDA:BHF-UCL.
DR GO; GO:0006626; P:protein targeting to mitochondrion; TAS:HGNC-UCL.
DR InterPro; IPR005683; Tom22.
DR PANTHER; PTHR12504; PTHR12504; 1.
DR Pfam; PF04281; Tom22; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Direct protein sequencing; Membrane;
KW Mitochondrion; Mitochondrion outer membrane; Phosphoprotein;
KW Protein transport; Receptor; Reference proteome; Translocation;
KW Transmembrane; Transmembrane helix; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:25944712"
FT CHAIN 2..142
FT /note="Mitochondrial import receptor subunit TOM22 homolog"
FT /id="PRO_0000076106"
FT TOPO_DOM 2..83
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 84..103
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 104..142
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT REGION 1..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 41..50
FT /note="Import sequence; necessary for mitochondrion outer
FT membrane localization and integration in the TOM complex"
FT /evidence="ECO:0000250"
FT REGION 83..103
FT /note="TMD; necessary for mitochondrion outer membrane
FT localization and integration in the TOM complex"
FT /evidence="ECO:0000250"
FT REGION 123..142
FT /note="C-tail signal; necessary for mitochondrion outer
FT membrane localization and integration in the TOM complex"
FT /evidence="ECO:0000250"
FT COMPBIAS 28..42
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:25944712"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 43
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 45
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9CPQ3"
FT HELIX 30..38
FT /evidence="ECO:0007829|PDB:7CP9"
FT HELIX 45..54
FT /evidence="ECO:0007829|PDB:7CP9"
FT STRAND 55..58
FT /evidence="ECO:0007829|PDB:7CP9"
FT HELIX 59..95
FT /evidence="ECO:0007829|PDB:7CP9"
FT HELIX 97..116
FT /evidence="ECO:0007829|PDB:7CP9"
SQ SEQUENCE 142 AA; 15522 MW; C957232F8420F34D CRC64;
MAAAVAAAGA GEPQSPDELL PKGDAEKPEE ELEEDDDEEL DETLSERLWG LTEMFPERVR
SAAGATFDLS LFVAQKMYRF SRAALWIGTT SFMILVLPVV FETEKLQMEQ QQQLQQRQIL
LGPNTGLSGG MPGALPSLPG KI
